A role for myelin-derived lipids in the induction of an anti-inflammatory phenotype in macrophages

Abstract

Multiple Sclerosis (MS) is an autoimmune disease, characterized by chronic inflammation and demyelination in the central nervous system (CNS). Macrophages (M') play a central role in the disease process of MS by phagocytosing myelin and releasing inflammatory and toxic mediators in the CNS. However, recent evidence has revealed the presence of a more M2, anti-inflammatory phenotype of M' in MS, especially following myelin phagocytosis. The myelin component inducing the M2 phenotype, however, is not yet known. We hypothesized that myelin-derived lipids may be responsible for the M2 phenotype. Indeed, phosphatidylserine (PS), a myelin-derived lipid induces an M2 phenotype in macrophages. Moreover, PS loaded liposome administration in an in vivo chronic EAE rat model resulted in significantly lower EAE scores and weight loss compared to control animals. These results suggest that PS loaded liposomes are likely to have a therapeutic effect in inflammatory diseases such as EAE and MS.